chr14-26452964-T-G

Variant names:

• chr14-26452964-T-G
• rs178228
• NM_002515.3:c.520-4001A>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_002515.3(NOVA1):​c.520-4001A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: NOVA1 NM_002515.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.72
• Publications: 0 publications found

Genes affected

NOVA1 (HGNC:7886): (NOVA alternative splicing regulator 1) This gene encodes a neuron-specific RNA-binding protein, a member of the Nova family of paraneoplastic disease antigens, that is recognized and inhibited by paraneoplastic antibodies. These antibodies are found in the sera of patients with paraneoplastic opsoclonus-ataxia, breast cancer, and small cell lung cancer. Alternatively spliced transcripts encoding distinct isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002515.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA1	NM_002515.3	MANE Select	c.520-4001A>C		intron	N/A	NP_002506.2
	NOVA1	NM_001366392.2		c.517-4001A>C		intron	N/A	NP_001353321.1
	NOVA1	NM_006489.3		c.448-4001A>C		intron	N/A	NP_006480.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NOVA1	ENST00000539517.7	TSL:1 MANE Select	c.520-4001A>C		intron	N/A	ENSP00000438875.2
	NOVA1	ENST00000483536.6	TSL:1	n.*256-4001A>C		intron	N/A	ENSP00000448956.1
	NOVA1	ENST00000465357.6	TSL:3	c.448-4001A>C		intron	N/A	ENSP00000447391.1

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.099
DANN	Benign	0.67
PhyloP100		-3.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs178228; hg19: chr14-26922170;